Difference between revisions of "Urothelial carcinoma - historical"
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[[#top|Back to Top]] | [[#top|Back to Top]] | ||
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− | The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only | + | The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. Is there a regimen missing from this list? See the [[Urothelial carcinoma|main urothelial carcinoma page]] for current regimens. |
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=Neoadjuvant chemotherapy= | =Neoadjuvant chemotherapy= | ||
==Atezolizumab monotherapy {{#subobject:3cb963|Regimen=1}}== | ==Atezolizumab monotherapy {{#subobject:3cb963|Regimen=1}}== | ||
− | <div class="toccolours" style="background-color:# | + | <div class="toccolours" style="background-color:#ee6b6e"> |
===Regimen {{#subobject:7ae9e3|Variant=1}}=== | ===Regimen {{#subobject:7ae9e3|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
Line 95: | Line 34: | ||
</div></div> | </div></div> | ||
===References=== | ===References=== | ||
− | #'''ABACUS:''' Powles T, Kockx M, Rodriguez-Vida A, Duran I, Crabb SJ, Van Der Heijden MS, Szabados B, Pous AF, Gravis G, Herranz UA, Protheroe A, Ravaud A, Maillet D, Mendez MJ, Suarez C, Linch M, Prendergast A, van Dam PJ, Stanoeva D, Daelemans S, Mariathasan S, Tea JS, Mousa K, Banchereau R, Castellano D. Clinical efficacy and biomarker analysis of neoadjuvant atezolizumab in operable urothelial carcinoma in the ABACUS trial. Nat Med. 2019 Nov 4. [https://doi.org/10.1038/s41591-019-0628-7 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31686036/ PubMed] [https://clinicaltrials.gov/study/NCT02662309 NCT02662309] | + | #'''ABACUS:''' Powles T, Kockx M, Rodriguez-Vida A, Duran I, Crabb SJ, Van Der Heijden MS, Szabados B, Pous AF, Gravis G, Herranz UA, Protheroe A, Ravaud A, Maillet D, Mendez MJ, Suarez C, Linch M, Prendergast A, van Dam PJ, Stanoeva D, Daelemans S, Mariathasan S, Tea JS, Mousa K, Banchereau R, Castellano D. Clinical efficacy and biomarker analysis of neoadjuvant atezolizumab in operable urothelial carcinoma in the ABACUS trial. Nat Med. 2019 Nov;25(11):1706-1714. Epub 2019 Nov 4. [https://doi.org/10.1038/s41591-019-0628-7 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31686036/ PubMed] [https://clinicaltrials.gov/study/NCT02662309 NCT02662309] |
+ | |||
=Locally advanced or metastatic disease, first-line, platinum-ineligible= | =Locally advanced or metastatic disease, first-line, platinum-ineligible= | ||
==Atezolizumab monotherapy {{#subobject:1d9e29|Regimen=1}}== | ==Atezolizumab monotherapy {{#subobject:1d9e29|Regimen=1}}== | ||
− | <div class="toccolours" style="background-color:# | + | <div class="toccolours" style="background-color:#ee6b6e"> |
===Regimen {{#subobject:764948|Variant=1}}=== | ===Regimen {{#subobject:764948|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 80%; text-align:center;" | {| class="wikitable sortable" style="width: 80%; text-align:center;" | ||
Line 107: | Line 47: | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5568632/ Balar et al. 2016 (IMvigor210 untreated)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5568632/ Balar et al. 2016 (IMvigor210 untreated)] | ||
− | {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | + | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" |
|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-355-1 <span style="color:white;">ESMO-MCBS (3)</span>]''' | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-355-1 <span style="color:white;">ESMO-MCBS (3)</span>]''' | ||
|- | |- | ||
− | |} | + | |} --> |
|2014-2015 | |2014-2015 | ||
| style="background-color:#91cf61" |Phase 2 (RT) | | style="background-color:#91cf61" |Phase 2 (RT) | ||
Line 125: | Line 65: | ||
=Locally advanced or metastatic disease, first-line, platinum-eligible= | =Locally advanced or metastatic disease, first-line, platinum-eligible= | ||
==Atezolizumab monotherapy {{#subobject:1d9e29|Regimen=1}}== | ==Atezolizumab monotherapy {{#subobject:1d9e29|Regimen=1}}== | ||
− | <div class="toccolours" style="background-color:# | + | <div class="toccolours" style="background-color:#ee6b6e"> |
===Regimen {{#subobject:764948|Variant=1}}=== | ===Regimen {{#subobject:764948|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 137: | Line 77: | ||
| rowspan="2" |2016-2018 | | rowspan="2" |2016-2018 | ||
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-switch-ooc) | | rowspan="2" style="background-color:#1a9851" |Phase 3 (E-switch-ooc) | ||
− | |1a. [[ | + | |1a. [[Urothelial_carcinoma#Carboplatin_.26_Gemcitabine_.28GCb.29|GCb]]<br>1b. [[Urothelial_carcinoma#Cisplatin_.26_Gemcitabine_.28GC.29_3|GC]] |
− | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | + | | style="background-color:#ffffbf" |Did not meet co-primary endpoint of OS |
|- | |- | ||
|2a. [[#Carboplatin_.26_Gemcitabine_.28GCb.29_.26_Atezolizumab|GCb & Atezolizumab]]<br>2b. [[#Cisplatin_.26_Gemcitabine_.28GC.29_.26_Atezolizumab|GC & Atezolizumab]] | |2a. [[#Carboplatin_.26_Gemcitabine_.28GCb.29_.26_Atezolizumab|GCb & Atezolizumab]]<br>2b. [[#Cisplatin_.26_Gemcitabine_.28GC.29_.26_Atezolizumab|GC & Atezolizumab]] | ||
Line 151: | Line 91: | ||
===References=== | ===References=== | ||
#'''IMvigor130:''' Galsky MD, Arranz Arija JÁ, Bamias A, Davis ID, De Santis M, Kikuchi E, Garcia-Del-Muro X, De Giorgi U, Mencinger M, Izumi K, Panni S, Gumus M, Özgüroğlu M, Kalebasty AR, Park SH, Alekseev B, Schutz FA, Li JR, Ye D, Vogelzang NJ, Bernhard S, Tayama D, Mariathasan S, Mecke A, Thåström A, Grande E; IMvigor130 Study Group. Atezolizumab with or without chemotherapy in metastatic urothelial cancer (IMvigor130): a multicentre, randomised, placebo-controlled phase 3 trial. Lancet. 2020 May 16;395(10236):1547-1557. [https://doi.org/10.1016/s0140-6736(20)30230-0 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32416780/ PubMed] [https://clinicaltrials.gov/study/NCT02807636 NCT02807636] | #'''IMvigor130:''' Galsky MD, Arranz Arija JÁ, Bamias A, Davis ID, De Santis M, Kikuchi E, Garcia-Del-Muro X, De Giorgi U, Mencinger M, Izumi K, Panni S, Gumus M, Özgüroğlu M, Kalebasty AR, Park SH, Alekseev B, Schutz FA, Li JR, Ye D, Vogelzang NJ, Bernhard S, Tayama D, Mariathasan S, Mecke A, Thåström A, Grande E; IMvigor130 Study Group. Atezolizumab with or without chemotherapy in metastatic urothelial cancer (IMvigor130): a multicentre, randomised, placebo-controlled phase 3 trial. Lancet. 2020 May 16;395(10236):1547-1557. [https://doi.org/10.1016/s0140-6736(20)30230-0 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32416780/ PubMed] [https://clinicaltrials.gov/study/NCT02807636 NCT02807636] | ||
+ | ##'''Update:''' Bamias A, Davis ID, Galsky MD, Arranz JÁ, Kikuchi E, Grande E, Del Muro XG, Park SH, De Giorgi U, Alekseev B, Mencinger M, Izumi K, Schutz FA, Puente J, Li JR, Panni S, Gumus M, Özgüroğlu M, Mariathasan S, Poloz Y, Bene-Tchaleu F, Lee C, Bernhard S, De Santis M. Atezolizumab monotherapy versus chemotherapy in untreated locally advanced or metastatic urothelial carcinoma (IMvigor130): final overall survival analysis from a randomised, controlled, phase 3 study. Lancet Oncol. 2024 Jan;25(1):46-61. Epub 2023 Dec 12. [https://doi.org/10.1016/S1470-2045(23)00539-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/38101431/ PubMed] | ||
+ | |||
==Carboplatin & Gemcitabine (GCb) & Atezolizumab {{#subobject:8tqccz|Regimen=1}}== | ==Carboplatin & Gemcitabine (GCb) & Atezolizumab {{#subobject:8tqccz|Regimen=1}}== | ||
GCb & Atezolizumab: '''<u>G</u>'''emcitabine, '''<u>C</u>'''ar'''<u>b</u>'''oplatin, Atezolizumab | GCb & Atezolizumab: '''<u>G</u>'''emcitabine, '''<u>C</u>'''ar'''<u>b</u>'''oplatin, Atezolizumab | ||
− | <div class="toccolours" style="background-color:# | + | <div class="toccolours" style="background-color:#ee6b6e"> |
===Regimen {{#subobject:8q1jx8|Variant=1}}=== | ===Regimen {{#subobject:8q1jx8|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 168: | Line 110: | ||
| style="background-color:#d3d3d3" |Not reported | | style="background-color:#d3d3d3" |Not reported | ||
|- | |- | ||
− | |2a. [[ | + | |2a. [[Urothelial_carcinoma#Carboplatin_.26_Gemcitabine_.28GCb.29|GCb]]<br>2b. [[Urothelial_carcinoma#Cisplatin_.26_Gemcitabine_.28GC.29_3|GC]] |
− | | style="background-color:# | + | | style="background-color:#d9ef8b" |Might have superior OS<sup>1</sup> (co-primary endpoint)<br>Median OS: 16.1 vs 13.4 mo<br>(HR 0.85, 95% CI 0.73-1.00)<br><br>Seems to have superior PFS (co-primary endpoint)<br>Median PFS: 8.2 vs 6.3 mo<br>(sHR 0.82, 95% CI 0.70-0.96) |
|- | |- | ||
|} | |} | ||
+ | ''<sup>1</sup>Reported efficacy is based on the 2023 update; the p-value did not meet the predefined definition of statistical significance.'' | ||
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
Line 182: | Line 125: | ||
===References=== | ===References=== | ||
#'''IMvigor130:''' Galsky MD, Arranz Arija JÁ, Bamias A, Davis ID, De Santis M, Kikuchi E, Garcia-Del-Muro X, De Giorgi U, Mencinger M, Izumi K, Panni S, Gumus M, Özgüroğlu M, Kalebasty AR, Park SH, Alekseev B, Schutz FA, Li JR, Ye D, Vogelzang NJ, Bernhard S, Tayama D, Mariathasan S, Mecke A, Thåström A, Grande E; IMvigor130 Study Group. Atezolizumab with or without chemotherapy in metastatic urothelial cancer (IMvigor130): a multicentre, randomised, placebo-controlled phase 3 trial. Lancet. 2020 May 16;395(10236):1547-1557. [https://doi.org/10.1016/s0140-6736(20)30230-0 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32416780/ PubMed] [https://clinicaltrials.gov/study/NCT02807636 NCT02807636] | #'''IMvigor130:''' Galsky MD, Arranz Arija JÁ, Bamias A, Davis ID, De Santis M, Kikuchi E, Garcia-Del-Muro X, De Giorgi U, Mencinger M, Izumi K, Panni S, Gumus M, Özgüroğlu M, Kalebasty AR, Park SH, Alekseev B, Schutz FA, Li JR, Ye D, Vogelzang NJ, Bernhard S, Tayama D, Mariathasan S, Mecke A, Thåström A, Grande E; IMvigor130 Study Group. Atezolizumab with or without chemotherapy in metastatic urothelial cancer (IMvigor130): a multicentre, randomised, placebo-controlled phase 3 trial. Lancet. 2020 May 16;395(10236):1547-1557. [https://doi.org/10.1016/s0140-6736(20)30230-0 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32416780/ PubMed] [https://clinicaltrials.gov/study/NCT02807636 NCT02807636] | ||
+ | ##'''Update:''' Grande E, Arranz JÁ, De Santis M, Bamias A, Kikuchi E, Del Muro XG, Park SH, De Giorgi U, Alekseev B, Mencinger M, Izumi K, Schutz FA, Puente J, Li JR, O'Donnell PH, Kalebasty AR, Ye D, Mariathasan S, Bene-Tchaleu F, Bernhard S, Lee C, Davis ID, Galsky MD. Atezolizumab plus chemotherapy versus placebo plus chemotherapy in untreated locally advanced or metastatic urothelial carcinoma (IMvigor130): final overall survival analysis results from a randomised, controlled, phase 3 study. Lancet Oncol. 2024 Jan;25(1):29-45. Epub 2023 Dec 12. [https://doi.org/10.1016/s1470-2045(23)00540-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/38101433/ PubMed] | ||
+ | ==CISCA {{#subobject:b60f2a|Regimen=1}}== | ||
+ | CISCA: '''<u>CIS</u>'''platin, '''<u>C</u>'''yclophosphamide, '''<u>A</u>'''driamycin (Doxorubicin) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:2d0b5e|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | ! style="width: 20%" |Study | ||
+ | ! style="width: 20%" |Dates of enrollment | ||
+ | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | ! style="width: 20%" |Comparator | ||
+ | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1001/jama.1977.03280220050021 Sternberg et al. 1977] | ||
+ | |1976-1977 | ||
+ | | style="background-color:#ffffbe" |Non-randomized, fewer than 20 pts | ||
+ | | style="background-color:#d3d3d3" | | ||
+ | | style="background-color:#d3d3d3" | | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/jco.1990.8.6.1050 Logothetis et al. 1990] | ||
+ | |1985-1989 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | ||
+ | |[[#MVAC_2|MVAC]] | ||
+ | | style="background-color:#d73027" |Inferior OS | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: ORR for this arm of Logothetis et al. 1990 was 46% (95% CI 32-62) versus 65% (95% CI 52-77) in the control arm.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Cyclophosphamide (Cytoxan)]] 650 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once on day 2 | ||
+ | *[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 2 | ||
+ | ====Supportive therapy==== | ||
+ | *Forced mannitol diuresis with cisplatin | ||
+ | '''21-day cycle for up to 6 cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | #Sternberg JJ, Bracken RB, Handel PB, Johnson DE. Combination chemotherapy (CISCA) for advanced urinary tract carcinoma: a preliminary report. JAMA. 1977 Nov 21;238(21):2282-7. [https://doi.org/10.1001/jama.1977.03280220050021 link to original article] [https://pubmed.ncbi.nlm.nih.gov/578848/ PubMed] | ||
+ | #Logothetis CJ, Dexeus FH, Finn L, Sella A, Amato RJ, Ayala AG, Kilbourn RG. A prospective randomized trial comparing MVAC and CISCA chemotherapy for patients with metastatic urothelial tumors. J Clin Oncol. 1990 Jun;8(6):1050-5. [https://doi.org/10.1200/jco.1990.8.6.1050 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/2189954/ PubMed] | ||
==Cisplatin monotherapy {{#subobject:1af7a9|Regimen=1}}== | ==Cisplatin monotherapy {{#subobject:1af7a9|Regimen=1}}== | ||
− | <div class="toccolours" style="background-color:# | + | <div class="toccolours" style="background-color:#ee6b6e"> |
===Regimen variant #1, 70 mg/m<sup>2</sup> {{#subobject:71bd05|Variant=1}}=== | ===Regimen variant #1, 70 mg/m<sup>2</sup> {{#subobject:71bd05|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 213: | Line 194: | ||
|1984-1989 | |1984-1989 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
− | |[[ | + | |[[Urothelial_carcinoma#MVAC_2|MVAC]] |
| style="background-color:#d73027" |Inferior OS | | style="background-color:#d73027" |Inferior OS | ||
|- | |- | ||
Line 223: | Line 204: | ||
'''28-day cycle for up to 6 cycles''' | '''28-day cycle for up to 6 cycles''' | ||
</div></div><br> | </div></div><br> | ||
− | <div class="toccolours" style="background-color:# | + | <div class="toccolours" style="background-color:#ee6b6e"> |
===Regimen variant #2, 80 mg/m<sup>2</sup> {{#subobject:8gbd05|Variant=1}}=== | ===Regimen variant #2, 80 mg/m<sup>2</sup> {{#subobject:8gbd05|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 255: | Line 236: | ||
==Cisplatin & Gemcitabine (GC) & Atezolizumab {{#subobject:8gajcz|Regimen=1}}== | ==Cisplatin & Gemcitabine (GC) & Atezolizumab {{#subobject:8gajcz|Regimen=1}}== | ||
GC & Atezolizumab: '''<u>G</u>'''emcitabine, '''<u>C</u>'''isplatin, Atezolizumab | GC & Atezolizumab: '''<u>G</u>'''emcitabine, '''<u>C</u>'''isplatin, Atezolizumab | ||
− | <div class="toccolours" style="background-color:# | + | <div class="toccolours" style="background-color:#ee6b6e"> |
===Regimen {{#subobject:80ihjx8|Variant=1}}=== | ===Regimen {{#subobject:80ihjx8|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 270: | Line 251: | ||
| style="background-color:#d3d3d3" |Not reported | | style="background-color:#d3d3d3" |Not reported | ||
|- | |- | ||
− | |2a. [[ | + | |2a. [[Urothelial_carcinoma#Carboplatin_.26_Gemcitabine_.28GCb.29|GCb]]<br>2b. [[Urothelial_carcinoma#Cisplatin_.26_Gemcitabine_.28GC.29_3|GC]] |
− | | style="background-color:# | + | | style="background-color:#d9ef8b" |Might have superior OS<sup>1</sup> (co-primary endpoint)<br>Median OS: 16.1 vs 13.4 mo<br>(HR 0.85, 95% CI 0.73-1.00)<br><br>Seems to have superior PFS (co-primary endpoint)<br>Median PFS: 8.2 vs 6.3 mo<br>(sHR 0.82, 95% CI 0.70-0.96) |
|- | |- | ||
|} | |} | ||
+ | ''<sup>1</sup>Reported efficacy is based on the 2023 update; the p-value did not meet the predefined definition of statistical significance.'' | ||
<div class="toccolours" style="background-color:#b3e2cd"> | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
Line 284: | Line 266: | ||
===References=== | ===References=== | ||
#'''IMvigor130:''' Galsky MD, Arranz Arija JÁ, Bamias A, Davis ID, De Santis M, Kikuchi E, Garcia-Del-Muro X, De Giorgi U, Mencinger M, Izumi K, Panni S, Gumus M, Özgüroğlu M, Kalebasty AR, Park SH, Alekseev B, Schutz FA, Li JR, Ye D, Vogelzang NJ, Bernhard S, Tayama D, Mariathasan S, Mecke A, Thåström A, Grande E; IMvigor130 Study Group. Atezolizumab with or without chemotherapy in metastatic urothelial cancer (IMvigor130): a multicentre, randomised, placebo-controlled phase 3 trial. Lancet. 2020 May 16;395(10236):1547-1557. [https://doi.org/10.1016/s0140-6736(20)30230-0 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32416780/ PubMed] [https://clinicaltrials.gov/study/NCT02807636 NCT02807636] | #'''IMvigor130:''' Galsky MD, Arranz Arija JÁ, Bamias A, Davis ID, De Santis M, Kikuchi E, Garcia-Del-Muro X, De Giorgi U, Mencinger M, Izumi K, Panni S, Gumus M, Özgüroğlu M, Kalebasty AR, Park SH, Alekseev B, Schutz FA, Li JR, Ye D, Vogelzang NJ, Bernhard S, Tayama D, Mariathasan S, Mecke A, Thåström A, Grande E; IMvigor130 Study Group. Atezolizumab with or without chemotherapy in metastatic urothelial cancer (IMvigor130): a multicentre, randomised, placebo-controlled phase 3 trial. Lancet. 2020 May 16;395(10236):1547-1557. [https://doi.org/10.1016/s0140-6736(20)30230-0 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32416780/ PubMed] [https://clinicaltrials.gov/study/NCT02807636 NCT02807636] | ||
+ | ##'''Update:''' Grande E, Arranz JÁ, De Santis M, Bamias A, Kikuchi E, Del Muro XG, Park SH, De Giorgi U, Alekseev B, Mencinger M, Izumi K, Schutz FA, Puente J, Li JR, O'Donnell PH, Kalebasty AR, Ye D, Mariathasan S, Bene-Tchaleu F, Bernhard S, Lee C, Davis ID, Galsky MD. Atezolizumab plus chemotherapy versus placebo plus chemotherapy in untreated locally advanced or metastatic urothelial carcinoma (IMvigor130): final overall survival analysis results from a randomised, controlled, phase 3 study. Lancet Oncol. 2024 Jan;25(1):29-45. Epub 2023 Dec 12. [https://doi.org/10.1016/s1470-2045(23)00540-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/38101433/ PubMed] | ||
==Durvalumab & Tremelimumab {{#subobject:5uckl3|Regimen=1}}== | ==Durvalumab & Tremelimumab {{#subobject:5uckl3|Regimen=1}}== | ||
− | <div class="toccolours" style="background-color:# | + | <div class="toccolours" style="background-color:#ee6b6e"> |
===Regimen {{#subobject:639ea8|Variant=1}}=== | ===Regimen {{#subobject:639ea8|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
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| rowspan="2" |2015-2017 | | rowspan="2" |2015-2017 | ||
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-switch-ooc) | | rowspan="2" style="background-color:#1a9851" |Phase 3 (E-switch-ooc) | ||
− | |1a. [[ | + | |1a. [[Urothelial_carcinoma#Carboplatin_.26_Gemcitabine_.28GCb.29|GCb]]<br>1b. [[Urothelial_carcinoma#Cisplatin_.26_Gemcitabine_.28GC.29_3|GC]] |
| style="background-color:#d9ef8b" |Might have superior OS (co-primary endpoint)<br>Median OS: 15.1 vs 12.1 mo<br>(HR 0.85, 95% CI 0.72-1.02) | | style="background-color:#d9ef8b" |Might have superior OS (co-primary endpoint)<br>Median OS: 15.1 vs 12.1 mo<br>(HR 0.85, 95% CI 0.72-1.02) | ||
|- | |- | ||
Line 317: | Line 300: | ||
=Metastatic disease, platinum-refractory= | =Metastatic disease, platinum-refractory= | ||
==Atezolizumab monotherapy {{#subobject:451e68|Regimen=1}}== | ==Atezolizumab monotherapy {{#subobject:451e68|Regimen=1}}== | ||
− | <div class="toccolours" style="background-color:# | + | <div class="toccolours" style="background-color:#ee6b6e"> |
===Regimen {{#subobject:feb2e2|Variant=1}}=== | ===Regimen {{#subobject:feb2e2|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 326: | Line 309: | ||
! style="width: 20%" |[[Levels of Evidence#Comparative efficacy|Comparative Efficacy]] | ! style="width: 20%" |[[Levels of Evidence#Comparative efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1038/nature13904 Powles et al. 2014 (PCD4989g)] |
|2013-2014 | |2013-2014 | ||
| style="background-color:#ffffbe" |Phase 1 | | style="background-color:#ffffbe" |Phase 1 | ||
Line 333: | Line 316: | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5480242/ Rosenberg et al. 2016 (IMvigor210 previously treated)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5480242/ Rosenberg et al. 2016 (IMvigor210 previously treated)] | ||
− | {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | + | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" |
|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-273-1 <span style="color:white;">ESMO-MCBS (1)</span>]''' | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-273-1 <span style="color:white;">ESMO-MCBS (1)</span>]''' | ||
|- | |- | ||
− | |} | + | |} --> |
|2014 | |2014 | ||
| style="background-color:#91cf61" |Phase 2 (RT) | | style="background-color:#91cf61" |Phase 2 (RT) | ||
Line 345: | Line 328: | ||
|2015-01-13 to 2016-02-15 | |2015-01-13 to 2016-02-15 | ||
| style="background-color:#1a9851" |Phase 3 (E-switch-ooc) | | style="background-color:#1a9851" |Phase 3 (E-switch-ooc) | ||
− | |1a. [[ | + | |1a. [[Urothelial_carcinoma#Docetaxel monotherapy|Docetaxel]]<br>1b. [[Urothelial_carcinoma#Paclitaxel monotherapy|Paclitaxel]]<br> 1c. [[Urothelial_carcinoma#Vinflunine monotherapy|Vinflunine]] |
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | ||
|- | |- | ||
Line 362: | Line 345: | ||
</div></div> | </div></div> | ||
===References=== | ===References=== | ||
− | #'''PCD4989g:''' Powles T, Eder JP, Fine GD, Braiteh FS, Loriot Y, Cruz C, Bellmunt J, Burris HA, Petrylak DP, Teng SL, Shen X, Boyd Z, Hegde PS, Chen DS, Vogelzang NJ. MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature. 2014 Nov 27;515(7528):558-62. [https:// | + | #'''PCD4989g:''' Powles T, Eder JP, Fine GD, Braiteh FS, Loriot Y, Cruz C, Bellmunt J, Burris HA, Petrylak DP, Teng SL, Shen X, Boyd Z, Hegde PS, Chen DS, Vogelzang NJ. MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature. 2014 Nov 27;515(7528):558-62. [https://doi.org/10.1038/nature13904 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25428503/ PubMed] [https://clinicaltrials.gov/study/NCT01375842 NCT01375842] |
#'''IMvigor210 previously treated:''' Rosenberg JE, Hoffman-Censits J, Powles T, van der Heijden MS, Balar AV, Necchi A, Dawson N, O'Donnell PH, Balmanoukian A, Loriot Y, Srinivas S, Retz MM, Grivas P, Joseph RW, Galsky MD, Fleming MT, Petrylak DP, Perez-Gracia JL, Burris HA, Castellano D, Canil C, Bellmunt J, Bajorin D, Nickles D, Bourgon R, Frampton GM, Cui N, Mariathasan S, Abidoye O, Fine GD, Dreicer R. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet. 2016 May 7;387(10031):1909-20. Epub 2016 Mar 4. [https://doi.org/10.1016/S0140-6736(16)00561-4 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5480242/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/26952546/ PubMed] [https://clinicaltrials.gov/study/NCT02108652 NCT02108652] | #'''IMvigor210 previously treated:''' Rosenberg JE, Hoffman-Censits J, Powles T, van der Heijden MS, Balar AV, Necchi A, Dawson N, O'Donnell PH, Balmanoukian A, Loriot Y, Srinivas S, Retz MM, Grivas P, Joseph RW, Galsky MD, Fleming MT, Petrylak DP, Perez-Gracia JL, Burris HA, Castellano D, Canil C, Bellmunt J, Bajorin D, Nickles D, Bourgon R, Frampton GM, Cui N, Mariathasan S, Abidoye O, Fine GD, Dreicer R. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet. 2016 May 7;387(10031):1909-20. Epub 2016 Mar 4. [https://doi.org/10.1016/S0140-6736(16)00561-4 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5480242/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/26952546/ PubMed] [https://clinicaltrials.gov/study/NCT02108652 NCT02108652] | ||
#'''IMvigor211:''' Powles T, Durán I, van der Heijden MS, Loriot Y, Vogelzang NJ, De Giorgi U, Oudard S, Retz MM, Castellano D, Bamias A, Fléchon A, Gravis G, Hussain S, Takano T, Leng N, Kadel EE 3rd, Banchereau R, Hegde PS, Mariathasan S, Cui N, Shen X, Derleth CL, Green MC, Ravaud A. Atezolizumab versus chemotherapy in patients with platinum-treated locally advanced or metastatic urothelial carcinoma (IMvigor211): a multicentre, open-label, phase 3 randomised controlled trial. Lancet. 2018 Feb 24;391(10122):748-757. Epub 2017 Dec 18. [https://doi.org/10.1016/S0140-6736(17)33297-X link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/29268948/ PubMed] [https://clinicaltrials.gov/study/NCT02302807 NCT02302807] | #'''IMvigor211:''' Powles T, Durán I, van der Heijden MS, Loriot Y, Vogelzang NJ, De Giorgi U, Oudard S, Retz MM, Castellano D, Bamias A, Fléchon A, Gravis G, Hussain S, Takano T, Leng N, Kadel EE 3rd, Banchereau R, Hegde PS, Mariathasan S, Cui N, Shen X, Derleth CL, Green MC, Ravaud A. Atezolizumab versus chemotherapy in patients with platinum-treated locally advanced or metastatic urothelial carcinoma (IMvigor211): a multicentre, open-label, phase 3 randomised controlled trial. Lancet. 2018 Feb 24;391(10122):748-757. Epub 2017 Dec 18. [https://doi.org/10.1016/S0140-6736(17)33297-X link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/29268948/ PubMed] [https://clinicaltrials.gov/study/NCT02302807 NCT02302807] | ||
==Durvalumab monotherapy {{#subobject:7ae7fb|Regimen=1}}== | ==Durvalumab monotherapy {{#subobject:7ae7fb|Regimen=1}}== | ||
− | <div class="toccolours" style="background-color:# | + | <div class="toccolours" style="background-color:#ee6b6e"> |
===Regimen {{#subobject:b2af36|Variant=1}}=== | ===Regimen {{#subobject:b2af36|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 80%; text-align:center;" | {| class="wikitable sortable" style="width: 80%; text-align:center;" | ||
Line 390: | Line 373: | ||
#'''Study 1108:''' Massard C, Gordon MS, Sharma S, Rafii S, Wainberg ZA, Luke J, Curiel TJ, Colon-Otero G, Hamid O, Sanborn RE, O'Donnell PH, Drakaki A, Tan W, Kurland JF, Rebelatto MC, Jin X, Blake-Haskins JA, Gupta A, Segal NH. Safety and efficacy of durvalumab (MEDI4736), an anti-programmed cell death ligand-1 immune checkpoint inhibitor, in patients with advanced urothelial bladder cancer. J Clin Oncol. 2016 Sep 10;34(26):3119-25. Epub 2016 Jun 6. [https://doi.org/10.1200/JCO.2016.67.9761 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5569690/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27269937/ PubMed] [https://clinicaltrials.gov/study/NCT01693562 NCT01693562] | #'''Study 1108:''' Massard C, Gordon MS, Sharma S, Rafii S, Wainberg ZA, Luke J, Curiel TJ, Colon-Otero G, Hamid O, Sanborn RE, O'Donnell PH, Drakaki A, Tan W, Kurland JF, Rebelatto MC, Jin X, Blake-Haskins JA, Gupta A, Segal NH. Safety and efficacy of durvalumab (MEDI4736), an anti-programmed cell death ligand-1 immune checkpoint inhibitor, in patients with advanced urothelial bladder cancer. J Clin Oncol. 2016 Sep 10;34(26):3119-25. Epub 2016 Jun 6. [https://doi.org/10.1200/JCO.2016.67.9761 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5569690/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27269937/ PubMed] [https://clinicaltrials.gov/study/NCT01693562 NCT01693562] | ||
##'''Update:''' Powles T, O'Donnell PH, Massard C, Arkenau HT, Friedlander TW, Hoimes CJ, Lee JL, Ong M, Sridhar SS, Vogelzang NJ, Fishman MN, Zhang J, Srinivas S, Parikh J, Antal J, Jin X, Gupta AK, Ben Y, Hahn NM. Efficacy and Safety of Durvalumab in Locally Advanced or Metastatic Urothelial Carcinoma: Updated Results From a Phase 1/2 Open-label Study. JAMA Oncol. 2017 Sep 14;3(9):e172411. Epub 2017 Sep 14. [https://doi.org/10.1001/jamaoncol.2017.2411 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5824288/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28817753/ PubMed] | ##'''Update:''' Powles T, O'Donnell PH, Massard C, Arkenau HT, Friedlander TW, Hoimes CJ, Lee JL, Ong M, Sridhar SS, Vogelzang NJ, Fishman MN, Zhang J, Srinivas S, Parikh J, Antal J, Jin X, Gupta AK, Ben Y, Hahn NM. Efficacy and Safety of Durvalumab in Locally Advanced or Metastatic Urothelial Carcinoma: Updated Results From a Phase 1/2 Open-label Study. JAMA Oncol. 2017 Sep 14;3(9):e172411. Epub 2017 Sep 14. [https://doi.org/10.1001/jamaoncol.2017.2411 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5824288/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28817753/ PubMed] | ||
− | [[Category: | + | [[Category:Urothelial carcinoma regimens]] |
[[Category:Historical regimens]] | [[Category:Historical regimens]] | ||
[[Category:Disease-specific pages]] | [[Category:Disease-specific pages]] | ||
[[Category:Genitourinary cancers]] | [[Category:Genitourinary cancers]] |
Latest revision as of 19:18, 28 June 2024
The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. Is there a regimen missing from this list? See the main urothelial carcinoma page for current regimens.
9 regimens on this page
10 variants on this page
|
Neoadjuvant chemotherapy
Atezolizumab monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Powles et al. 2019 (ABACUS) | 2016-2018 | Phase 2 |
Subsequent treatment
- Radical cystectomy to be performed 4 to 8 weeks after completion of chemotherapy
References
- ABACUS: Powles T, Kockx M, Rodriguez-Vida A, Duran I, Crabb SJ, Van Der Heijden MS, Szabados B, Pous AF, Gravis G, Herranz UA, Protheroe A, Ravaud A, Maillet D, Mendez MJ, Suarez C, Linch M, Prendergast A, van Dam PJ, Stanoeva D, Daelemans S, Mariathasan S, Tea JS, Mousa K, Banchereau R, Castellano D. Clinical efficacy and biomarker analysis of neoadjuvant atezolizumab in operable urothelial carcinoma in the ABACUS trial. Nat Med. 2019 Nov;25(11):1706-1714. Epub 2019 Nov 4. link to original article PubMed NCT02662309
Locally advanced or metastatic disease, first-line, platinum-ineligible
Atezolizumab monotherapy
Regimen
Study | Dates of enrollment | Evidence | Efficacy |
---|---|---|---|
Balar et al. 2016 (IMvigor210 untreated) | 2014-2015 | Phase 2 (RT) | ORR: 23% (95% CI 16-31) |
References
- IMvigor210 untreated: Balar AV, Galsky MD, Rosenberg JE, Powles T, Petrylak DP, Bellmunt J, Loriot Y, Necchi A, Hoffman-Censits J, Perez-Gracia JL, Dawson NA, van der Heijden MS, Dreicer R, Srinivas S, Retz MM, Joseph RW, Drakaki A, Vaishampayan UN, Sridhar SS, Quinn DI, Durán I, Shaffer DR, Eigl BJ, Grivas PD, Yu EY, Li S, Kadel EE 3rd, Boyd Z, Bourgon R, Hegde PS, Mariathasan S, Thåström A, Abidoye OO, Fine GD, Bajorin DF; IMvigor210 Study Group. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet. 2017 Jan 7;389(10064):67-76. Epub 2016 Dec 8. link to original article contains dosing details in abstract link to PMC article PubMed NCT02951767
Locally advanced or metastatic disease, first-line, platinum-eligible
Atezolizumab monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Galsky et al. 2020 (IMvigor130) | 2016-2018 | Phase 3 (E-switch-ooc) | 1a. GCb 1b. GC |
Did not meet co-primary endpoint of OS |
2a. GCb & Atezolizumab 2b. GC & Atezolizumab |
Not reported |
References
- IMvigor130: Galsky MD, Arranz Arija JÁ, Bamias A, Davis ID, De Santis M, Kikuchi E, Garcia-Del-Muro X, De Giorgi U, Mencinger M, Izumi K, Panni S, Gumus M, Özgüroğlu M, Kalebasty AR, Park SH, Alekseev B, Schutz FA, Li JR, Ye D, Vogelzang NJ, Bernhard S, Tayama D, Mariathasan S, Mecke A, Thåström A, Grande E; IMvigor130 Study Group. Atezolizumab with or without chemotherapy in metastatic urothelial cancer (IMvigor130): a multicentre, randomised, placebo-controlled phase 3 trial. Lancet. 2020 May 16;395(10236):1547-1557. link to original article contains dosing details in manuscript PubMed NCT02807636
- Update: Bamias A, Davis ID, Galsky MD, Arranz JÁ, Kikuchi E, Grande E, Del Muro XG, Park SH, De Giorgi U, Alekseev B, Mencinger M, Izumi K, Schutz FA, Puente J, Li JR, Panni S, Gumus M, Özgüroğlu M, Mariathasan S, Poloz Y, Bene-Tchaleu F, Lee C, Bernhard S, De Santis M. Atezolizumab monotherapy versus chemotherapy in untreated locally advanced or metastatic urothelial carcinoma (IMvigor130): final overall survival analysis from a randomised, controlled, phase 3 study. Lancet Oncol. 2024 Jan;25(1):46-61. Epub 2023 Dec 12. link to original article PubMed
Carboplatin & Gemcitabine (GCb) & Atezolizumab
GCb & Atezolizumab: Gemcitabine, Carboplatin, Atezolizumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Galsky et al. 2020 (IMvigor130) | 2016-2018 | Phase 3 (E-RT-esc) | 1. Atezolizumab | Not reported |
2a. GCb 2b. GC |
Might have superior OS1 (co-primary endpoint) Median OS: 16.1 vs 13.4 mo (HR 0.85, 95% CI 0.73-1.00) Seems to have superior PFS (co-primary endpoint) Median PFS: 8.2 vs 6.3 mo (sHR 0.82, 95% CI 0.70-0.96) |
1Reported efficacy is based on the 2023 update; the p-value did not meet the predefined definition of statistical significance.
Chemotherapy
- Carboplatin (Paraplatin) AUC 4.5 IV once on day 1
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
Immunotherapy
- Atezolizumab (Tecentriq) 1200 mg IV once on day 1
21-day cycles
References
- IMvigor130: Galsky MD, Arranz Arija JÁ, Bamias A, Davis ID, De Santis M, Kikuchi E, Garcia-Del-Muro X, De Giorgi U, Mencinger M, Izumi K, Panni S, Gumus M, Özgüroğlu M, Kalebasty AR, Park SH, Alekseev B, Schutz FA, Li JR, Ye D, Vogelzang NJ, Bernhard S, Tayama D, Mariathasan S, Mecke A, Thåström A, Grande E; IMvigor130 Study Group. Atezolizumab with or without chemotherapy in metastatic urothelial cancer (IMvigor130): a multicentre, randomised, placebo-controlled phase 3 trial. Lancet. 2020 May 16;395(10236):1547-1557. link to original article contains dosing details in manuscript PubMed NCT02807636
- Update: Grande E, Arranz JÁ, De Santis M, Bamias A, Kikuchi E, Del Muro XG, Park SH, De Giorgi U, Alekseev B, Mencinger M, Izumi K, Schutz FA, Puente J, Li JR, O'Donnell PH, Kalebasty AR, Ye D, Mariathasan S, Bene-Tchaleu F, Bernhard S, Lee C, Davis ID, Galsky MD. Atezolizumab plus chemotherapy versus placebo plus chemotherapy in untreated locally advanced or metastatic urothelial carcinoma (IMvigor130): final overall survival analysis results from a randomised, controlled, phase 3 study. Lancet Oncol. 2024 Jan;25(1):29-45. Epub 2023 Dec 12. link to original article PubMed
CISCA
CISCA: CISplatin, Cyclophosphamide, Adriamycin (Doxorubicin)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sternberg et al. 1977 | 1976-1977 | Non-randomized, fewer than 20 pts | ||
Logothetis et al. 1990 | 1985-1989 | Phase 3 (E-switch-ic) | MVAC | Inferior OS |
Note: ORR for this arm of Logothetis et al. 1990 was 46% (95% CI 32-62) versus 65% (95% CI 52-77) in the control arm.
Chemotherapy
- Cyclophosphamide (Cytoxan) 650 mg/m2 IV once on day 1
- Cisplatin (Platinol) 100 mg/m2 IV once on day 2
- Doxorubicin (Adriamycin) 50 mg/m2 IV once on day 2
Supportive therapy
- Forced mannitol diuresis with cisplatin
21-day cycle for up to 6 cycles
References
- Sternberg JJ, Bracken RB, Handel PB, Johnson DE. Combination chemotherapy (CISCA) for advanced urinary tract carcinoma: a preliminary report. JAMA. 1977 Nov 21;238(21):2282-7. link to original article PubMed
- Logothetis CJ, Dexeus FH, Finn L, Sella A, Amato RJ, Ayala AG, Kilbourn RG. A prospective randomized trial comparing MVAC and CISCA chemotherapy for patients with metastatic urothelial tumors. J Clin Oncol. 1990 Jun;8(6):1050-5. link to original article contains dosing details in manuscript PubMed
Cisplatin monotherapy
Regimen variant #1, 70 mg/m2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Soloway et al. 1983 | 1978-NR | Randomized (C) | Cisplatin & Cyclophosphamide | Did not meet primary endpoint of ORR |
Khandekar et al. 1985 | 1978-1981 | Randomized (C) | CAD | Might have inferior ORR |
Troner et al. 1987 | NR | Phase 3 (C) | CAD | Did not meet endpoint of ORR |
Loehrer et al. 1992 (ECOG E5886) | 1984-1989 | Phase 3 (C) | MVAC | Inferior OS |
Note: To our knowledge, this regimen was not tested as an experimental arm in a RCT prior to becoming a standard comparator arm.
Regimen variant #2, 80 mg/m2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Hillcoat et al. 1989 | 1982-1986 | Phase 3 (C) | Cisplatin & Methotrexate | Did not meet efficacy endpoints |
Note: To our knowledge, this regimen was not tested as an experimental arm in a RCT prior to becoming a standard comparator arm.
References
- Soloway MS, Einstein A, Corder MP, Bonney W, Prout GR Jr, Coombs J; National Bladder Cancer Collaborative Group A. A comparison of cisplatin and the combination of cisplatin and cyclophosphamide in advanced urothelial cancer: a National Bladder Cancer Collaborative Group A study. Cancer. 1983 Sep 1;52(5):767-72. link to original article PubMed
- Khandekar JD, Elson PJ, DeWys WD, Slayton RE, Harris DT. Comparative activity and toxicity of cis-diamminedichloroplatinum (DDP) and a combination of doxorubicin, cyclophosphamide, and DDP in disseminated transitional cell carcinomas of the urinary tract. J Clin Oncol. 1985 Apr;3(4):539-45. link to original article PubMed
- Troner M, Birch R, Omura GA, Williams S; Southeastern Cancer Study Group. Phase III comparison of cisplatin alone versus cisplatin, doxorubicin and cyclophosphamide in the treatment of bladder (urothelial) cancer: a Southeastern Cancer Study Group trial. J Urol. 1987 Apr;137(4):660-2. link to original article PubMed
- Hillcoat BL, Raghavan D, Matthews J, Kefford R, Yuen K, Woods R, Olver I, Bishop J, Pearson B, Coorey G, Levi J, Abbott RL, Aroney R, Gill PG, McLennan R. A randomized trial of cisplatin versus cisplatin plus methotrexate in advanced cancer of the urothelial tract. J Clin Oncol. 1989 Jun;7(6):706-9. link to original article contains dosing details in abstract PubMed
- ECOG E5886: Loehrer PJ Sr, Einhorn LH, Elson PJ, Crawford ED, Kuebler P, Tannock I, Raghavan D, Stuart-Harris R, Sarosdy MF, Lowe BA, Blumenstein B, Trump D. A randomized comparison of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: a cooperative group study. J Clin Oncol. 1992 Jul;10(7):1066-73. Erratum in: J Clin Oncol 1993 Feb;11(2):384. link to original article contains dosing details in manuscript PubMed
- Update: Saxman SB, Propert KJ, Einhorn LH, Crawford ED, Tannock I, Raghavan D, Loehrer PJ Sr, Trump D. Long-term follow-up of a phase III intergroup study of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: a cooperative group study. J Clin Oncol. 1997 Jul;15(7):2564-9. link to original article PubMed
Cisplatin & Gemcitabine (GC) & Atezolizumab
GC & Atezolizumab: Gemcitabine, Cisplatin, Atezolizumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Galsky et al. 2020 (IMvigor130) | 2016-2018 | Phase 3 (E-RT-esc) | 1. Atezolizumab | Not reported |
2a. GCb 2b. GC |
Might have superior OS1 (co-primary endpoint) Median OS: 16.1 vs 13.4 mo (HR 0.85, 95% CI 0.73-1.00) Seems to have superior PFS (co-primary endpoint) Median PFS: 8.2 vs 6.3 mo (sHR 0.82, 95% CI 0.70-0.96) |
1Reported efficacy is based on the 2023 update; the p-value did not meet the predefined definition of statistical significance.
Chemotherapy
- Cisplatin (Platinol) 70 mg/m2 IV once on day 1
- Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1 & 8
Immunotherapy
- Atezolizumab (Tecentriq) 1200 mg IV once on day 1
21-day cycles
References
- IMvigor130: Galsky MD, Arranz Arija JÁ, Bamias A, Davis ID, De Santis M, Kikuchi E, Garcia-Del-Muro X, De Giorgi U, Mencinger M, Izumi K, Panni S, Gumus M, Özgüroğlu M, Kalebasty AR, Park SH, Alekseev B, Schutz FA, Li JR, Ye D, Vogelzang NJ, Bernhard S, Tayama D, Mariathasan S, Mecke A, Thåström A, Grande E; IMvigor130 Study Group. Atezolizumab with or without chemotherapy in metastatic urothelial cancer (IMvigor130): a multicentre, randomised, placebo-controlled phase 3 trial. Lancet. 2020 May 16;395(10236):1547-1557. link to original article contains dosing details in manuscript PubMed NCT02807636
- Update: Grande E, Arranz JÁ, De Santis M, Bamias A, Kikuchi E, Del Muro XG, Park SH, De Giorgi U, Alekseev B, Mencinger M, Izumi K, Schutz FA, Puente J, Li JR, O'Donnell PH, Kalebasty AR, Ye D, Mariathasan S, Bene-Tchaleu F, Bernhard S, Lee C, Davis ID, Galsky MD. Atezolizumab plus chemotherapy versus placebo plus chemotherapy in untreated locally advanced or metastatic urothelial carcinoma (IMvigor130): final overall survival analysis results from a randomised, controlled, phase 3 study. Lancet Oncol. 2024 Jan;25(1):29-45. Epub 2023 Dec 12. link to original article PubMed
Durvalumab & Tremelimumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Powles et al. 2020 (DANUBE) | 2015-2017 | Phase 3 (E-switch-ooc) | 1a. GCb 1b. GC |
Might have superior OS (co-primary endpoint) Median OS: 15.1 vs 12.1 mo (HR 0.85, 95% CI 0.72-1.02) |
2. Durvalumab | Not reported |
Immunotherapy
- Durvalumab (Imfinzi) 1500 mg IV once on day 1
- Tremelimumab (Imjudo) as follows:
- Cycles 1 to 4: 75 mg IV once on day 1
28-day cycles
References
- DANUBE: Powles T, van der Heijden MS, Castellano D, Galsky MD, Loriot Y, Petrylak DP, Ogawa O, Park SH, Lee JL, De Giorgi U, Bögemann M, Bamias A, Eigl BJ, Gurney H, Mukherjee SD, Fradet Y, Skoneczna I, Tsiatas M, Novikov A, Suárez C, Fay AP, Duran I, Necchi A, Wildsmith S, He P, Angra N, Gupta AK, Levin W, Bellmunt J; DANUBE study investigators. Durvalumab alone and durvalumab plus tremelimumab versus chemotherapy in previously untreated patients with unresectable, locally advanced or metastatic urothelial carcinoma (DANUBE): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2020 Dec;21(12):1574-1588. Epub 2020 Sep 21. link to original article contains dosing details in abstract PubMed NCT02516241
Metastatic disease, platinum-refractory
Atezolizumab monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Powles et al. 2014 (PCD4989g) | 2013-2014 | Phase 1 | ||
Rosenberg et al. 2016 (IMvigor210 previously treated) | 2014 | Phase 2 (RT) | ORR: 15% (95% CI 11-20) | |
Powles et al. 2017 (IMvigor211) | 2015-01-13 to 2016-02-15 | Phase 3 (E-switch-ooc) | 1a. Docetaxel 1b. Paclitaxel 1c. Vinflunine |
Did not meet primary endpoint of OS |
Note: this regimen did not meet its primary endpoint in phase 3; here for historical reference only.
Biomarker eligibility criteria
Patients are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 (PD-L1 stained tumor-infiltrating immune cells [IC] covering at least 5% of the tumor area), as determined by an FDA-approved test Patients are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status
References
- PCD4989g: Powles T, Eder JP, Fine GD, Braiteh FS, Loriot Y, Cruz C, Bellmunt J, Burris HA, Petrylak DP, Teng SL, Shen X, Boyd Z, Hegde PS, Chen DS, Vogelzang NJ. MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature. 2014 Nov 27;515(7528):558-62. link to original article PubMed NCT01375842
- IMvigor210 previously treated: Rosenberg JE, Hoffman-Censits J, Powles T, van der Heijden MS, Balar AV, Necchi A, Dawson N, O'Donnell PH, Balmanoukian A, Loriot Y, Srinivas S, Retz MM, Grivas P, Joseph RW, Galsky MD, Fleming MT, Petrylak DP, Perez-Gracia JL, Burris HA, Castellano D, Canil C, Bellmunt J, Bajorin D, Nickles D, Bourgon R, Frampton GM, Cui N, Mariathasan S, Abidoye O, Fine GD, Dreicer R. Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet. 2016 May 7;387(10031):1909-20. Epub 2016 Mar 4. link to original article link to PMC article contains dosing details in abstract PubMed NCT02108652
- IMvigor211: Powles T, Durán I, van der Heijden MS, Loriot Y, Vogelzang NJ, De Giorgi U, Oudard S, Retz MM, Castellano D, Bamias A, Fléchon A, Gravis G, Hussain S, Takano T, Leng N, Kadel EE 3rd, Banchereau R, Hegde PS, Mariathasan S, Cui N, Shen X, Derleth CL, Green MC, Ravaud A. Atezolizumab versus chemotherapy in patients with platinum-treated locally advanced or metastatic urothelial carcinoma (IMvigor211): a multicentre, open-label, phase 3 randomised controlled trial. Lancet. 2018 Feb 24;391(10122):748-757. Epub 2017 Dec 18. link to original article contains dosing details in abstract PubMed NCT02302807
Durvalumab monotherapy
Regimen
Study | Dates of enrollment | Evidence | Efficacy |
---|---|---|---|
Massard et al. 2016 (Study 1108) | 2014-2015 | Phase 1/2 (RT) | ORR: 31% (95% CI 18 to 47) |
Note: this regimen was intended for patients "who had progressed on, been ineligible for, or refused any number of prior therapies".
Immunotherapy
- Durvalumab (Imfinzi) 10 mg/kg IV over 60 minutes once on day 1
14-day cycle for up to 26 cycles (1 year). Patients could receive another 12 months of treatment if they experienced disease progression, had not received other anticancer treatment, and did not meet criteria for discontinuation.
References
- Study 1108: Massard C, Gordon MS, Sharma S, Rafii S, Wainberg ZA, Luke J, Curiel TJ, Colon-Otero G, Hamid O, Sanborn RE, O'Donnell PH, Drakaki A, Tan W, Kurland JF, Rebelatto MC, Jin X, Blake-Haskins JA, Gupta A, Segal NH. Safety and efficacy of durvalumab (MEDI4736), an anti-programmed cell death ligand-1 immune checkpoint inhibitor, in patients with advanced urothelial bladder cancer. J Clin Oncol. 2016 Sep 10;34(26):3119-25. Epub 2016 Jun 6. link to original article contains dosing details in abstract link to PMC article PubMed NCT01693562
- Update: Powles T, O'Donnell PH, Massard C, Arkenau HT, Friedlander TW, Hoimes CJ, Lee JL, Ong M, Sridhar SS, Vogelzang NJ, Fishman MN, Zhang J, Srinivas S, Parikh J, Antal J, Jin X, Gupta AK, Ben Y, Hahn NM. Efficacy and Safety of Durvalumab in Locally Advanced or Metastatic Urothelial Carcinoma: Updated Results From a Phase 1/2 Open-label Study. JAMA Oncol. 2017 Sep 14;3(9):e172411. Epub 2017 Sep 14. link to original article link to PMC article PubMed